A novel serogenetic approach determines the community prevalence of celiac disease and informs improved diagnostic pathways

Anderson, Robert P., Henry, Margaret J., Taylor, Roberta, Duncan, Emma L., Danoy, Patrick, Costa, Marylia J., Addison, Kathryn, Tye-Din, Jason A., Kotowicz, Mark A., Knight, Ross E., Pollock, Wendy, Nicholson, Geoffrey C., Toh, Ban-Hock, Brown, Matthew A. and Pasco, Julie A. (2013) A novel serogenetic approach determines the community prevalence of celiac disease and informs improved diagnostic pathways. BMC Medicine, 11 1: 188.1-188.13. doi:10.1186/1741-7015-11-188


Author Anderson, Robert P.
Henry, Margaret J.
Taylor, Roberta
Duncan, Emma L.
Danoy, Patrick
Costa, Marylia J.
Addison, Kathryn
Tye-Din, Jason A.
Kotowicz, Mark A.
Knight, Ross E.
Pollock, Wendy
Nicholson, Geoffrey C.
Toh, Ban-Hock
Brown, Matthew A.
Pasco, Julie A.
Title A novel serogenetic approach determines the community prevalence of celiac disease and informs improved diagnostic pathways
Journal name BMC Medicine   Check publisher's open access policy
ISSN 1741-7015
Publication date 2013-08
Year available 2013
Sub-type Article (original research)
DOI 10.1186/1741-7015-11-188
Open Access Status DOI
Volume 11
Issue 1
Start page 188.1
End page 188.13
Total pages 13
Place of publication London United Kingdom
Publisher BioMed Central
Collection year 2014
Language eng
Abstract Background Changing perspectives on the natural history of celiac disease (CD), new serology and genetic tests, and amended histological criteria for diagnosis cast doubt on past prevalence estimates for CD. We set out to establish a more accurate prevalence estimate for CD using a novel serogenetic approach. Methods The human leukocyte antigen (HLA)-DQ genotype was determined in 356 patients with ‘biopsy-confirmed’ CD, and in two age-stratified, randomly selected community cohorts of 1,390 women and 1,158 men. Sera were screened for CD-specific serology. Results Only five ‘biopsy-confirmed’ patients with CD did not possess the susceptibility alleles HLA-DQ2.5, DQ8, or DQ2.2, and four of these were misdiagnoses. HLA-DQ2.5, DQ8, or DQ2.2 was present in 56% of all women and men in the community cohorts. Transglutaminase (TG)-2 IgA and composite TG2/deamidated gliadin peptide (DGP) IgA/IgG were abnormal in 4.6% and 5.6%, respectively, of the community women and 6.9% and 6.9%, respectively, of the community men, but in the screen-positive group, only 71% and 75%, respectively, of women and 65% and 63%, respectively, of men possessed HLA-DQ2.5, DQ8, or DQ2.2. Medical review was possible for 41% of seropositive women and 50% of seropositive men, and led to biopsy-confirmed CD in 10 women (0.7%) and 6 men (0.5%), but based on relative risk for HLA-DQ2.5, DQ8, or DQ2.2 in all TG2 IgA or TG2/DGP IgA/IgG screen-positive subjects, CD affected 1.3% or 1.9%, respectively, of females and 1.3% or 1.2%, respectively, of men. Serogenetic data from these community cohorts indicated that testing screen positives for HLA-DQ, or carrying out HLA-DQ and further serology, could have reduced unnecessary gastroscopies due to false-positive serology by at least 40% and by over 70%, respectively. Conclusions Screening with TG2 IgA serology and requiring biopsy confirmation caused the community prevalence of CD to be substantially underestimated. Testing for HLA-DQ genes and confirmatory serology could reduce the numbers of unnecessary gastroscopies.
Keyword Celiac disease
Diagnosis
Epidemiology
Serology
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
UQ Diamantina Institute Publications
 
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